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Silencing of integrated human papillomavirus type 18 oncogene transcription in cells expressing SerpinB2

Grant A Darnell1, Toni M Antalis, Barbara R Rose

  • 1Queensland Institute of Medical Research, University of Queensland, Brisbane, Queensland, Australia.

Journal of Virology
|March 16, 2005
PubMed

Insights

Serine protease inhibitor SerpinB2 (PAI-2) restores retinoblastoma protein (Rb) expression in cervical cancer cells. This suppresses human papillomavirus type 18 (HPV-18) oncogene transcription, impacting treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Virology

Background:

  • Serine protease inhibitor SerpinB2 (PAI-2) protects the retinoblastoma protein (Rb) from degradation.
  • Human papillomavirus type 18 (HPV-18) oncoproteins E6 and E7 are regulated by the HPV-18 upstream regulatory region (URR).

Purpose of the Study:

  • To investigate the effect of PAI-2 expression on HPV-18 oncogene transcription in cervical carcinoma cells.
  • To elucidate the mechanism by which PAI-2 influences HPV-18 URR activity and host protein restoration.

Main Methods:

  • Introducing PAI-2 into HPV-18-transformed HeLa cells.
  • Analyzing Rb expression levels.
  • Assessing HPV-18 URR transcriptional activity.
  • Evaluating the binding of transcription factors to the HPV-18 URR.
  • Measuring the expression of E6, E7, p53, c-Myc, and c-Jun proteins.

Main Results:

  • PAI-2 expression restored Rb expression in HeLa cells.
  • Rb expression led to functional silencing of HPV-18 URR transcription.
  • Loss of E7 protein expression and restoration of p53, c-Myc, and c-Jun.
  • Repression of HPV-18 URR was mediated by the C/EBPbeta-YY1 binding site, occupied by the dominant-negative C/EBPbeta isoform LIP in PAI-2/Rb-expressing cells.

Conclusions:

  • PAI-2 exerts a potent suppressive effect on HPV-18 oncogene transcription via Rb and LIP.
  • This mechanism has potential implications for the prognosis and treatment of HPV-transformed lesions.

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